Expression pattern of MMP-12 in long-term optic nerve regeneration induced by lens injury / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression changes of MMP-12 during the long-term axon regeneration induced by the lens injury after the optic nerve clamp trauma in sprague-dawley(SD)rats.METHODS: The optic nerve injury model and lens injury model of SD rats were established, and the 24 experimental animals were divided into control group; lens injury group; optic nerve injury group; lens injury combined with optic nerve injury group, with 6 rats in each group. Reference transcriptome sequencing was used to analyze the expression changes of differentially expressed genes in the injured optic nerve region, and relevant differentially expressed genes with high expression were screened. Quantitative real-time polymerase chain reaction(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to quantify the expression changes of matrix metalloproteinase-12(MMP-12)in the injured optic nerve region.RESULTS: The Principal Component Analysis of transcriptome sequencing indicated that lens injury combined with optic nerve injury was the principal component of gene expression change. Analysis of gene expression differences showed that the expression of MMP-12 gene was up-regulated in the lens injury combined with optic nerve injury group. The mRNA expression level of MMP-12 in the lens injury combined optic nerve injury group was up-regulated compared with the control group, the optic nerve injury group and the lens injury group at 14d and 21d after successful modeling(P<0.05). At 7, 28d, there was no difference in expression among all groups. The protein expression level of MMP-12 in the lens injury combined with optic nerve injury group was up-regulated compared with the control group and optic nerve injury group at 7, 14 and 21d after successful modeling(P<0.05), and it was up-regulated in the lens injury group combined with optic nerve injury group compared with optic nerve injury group at 21d(P<0.05). At 28d, there was no difference in expression among all groups.CONCLUSION: The up-regulated expression of MMP-12 may be involved in the long-term regeneration of the optic nerve after lens injury.

Association between serum alkaline phosphatase and type 2 diabetes mellitus with nonalcoholic fatty liver disease / 临床肝胆病杂志

Objective To investigate the association between serum alkaline phosphatase (ALP) and type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Methods A total of 599 patients with T2DM who were hospitalized in Department of Endocrinology, Affiliated Hospital of Jiangsu University, from July 2016 to December 2018 were enrolled as subjects. According to the presence or absence of NAFLD, the patients were divided into NAFLD group with 286 patients and non-NAFLD group with 313 patients, and according to the results of abdominal ultrasound, the patients with NAFLD were divided into mild group with 111 patients, moderate group with 105 patients, and severe group with 70 patients. General clinical data were compared between groups. The independent samples t - test was used for comparison of normally distributed continuous data between two groups, and an analysis of variance was used for comparison between three groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups; the chi-square test was used for comparison of categorical data between groups. Pearson correlation analysis and Spearman correlation analysis were used to investigate the correlation between ALP and clinical indices, and a logistic regression analysis was used to investigate the influencing factors for NAFLD. Results Compared with the non-NAFLD group, the NAFLD group had significantly higher proportion of patients with history of hypertension ( χ 2 =7.864, P < 0.05), systolic blood pressure ( t =-2.226, P < 0.05), diastolic blood pressure ( t =-3.800, P < 0.05), body mass index (BMI) ( t =-11.842, P < 0.05), waist circumference (WC) ( t =-9.150, P < 0.05), fasting insulin (FINS) ( Z =-6.173, P < 0.05), fasting C-peptide ( t =-5.419, P < 0.05), serum uric acid ( t =-4.957, P < 0.05), low-density lipoprotein cholesterol ( t =-2.702, P < 0.05), triglyceride ( Z =-9.376, P < 0.05), total cholesterol (TC) ( t =-3.016, P < 0.05), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ( Z =-5.794, P < 0.05), alanine aminotransferase (ALT) ( Z =-6.737, P < 0.05), aspartate aminotransferase (AST) ( Z =-4.389, P < 0.05), gamma-glutamyl transpeptidase (GGT) ( Z =-7.764, P < 0.05), and ALP ( t =-2.833, P < 0.05), as well as significantly lower age ( t =2.184, P < 0.05) and high-density lipoprotein cholesterol ( Z =-5.273, P < 0.05). The severity of NAFLD (mild, moderate or severe) was positively correlated with age ( r s =0.140, P < 0.05), BMI ( r s =0.239, P < 0.05), WC ( r s =0.222, P < 0.05), FINS ( r s =0.191, P < 0.05), HOMA-IR ( r s =0.218, P < 0.05), ALT ( r s =0.188, P < 0.05), AST ( r s =0.279, P < 0.05), GGT ( r s =0.202, P < 0.05), and ALP ( r s =0.361, P < 0.05). In the patients with T2DM and NAFLD, ALP was positively correlated with HbAlc ( r =0.149, P < 0.05), fasting plasma glucose ( r =0.146, P < 0.05), HOMA-IR ( r s =0.132, P < 0.05), TC ( r =0.151, P < 0.05), ALT ( r s =0.210, P < 0.05), AST ( r s =0.192, P < 0.05), and GGT ( r s =0.297, P < 0.05). The logistic regression analysis showed that ALP was an influencing factor for NAFLD in patients with T2DM (odds ratio=1.013, 95% confidence interval: 1.004-1.023, P < 0.05). Conclusion Elevated serum ALP is a risk factor for T2DM with NAFLD and is closely associated with hyperglycemia, insulin resistance, and hyperlipemia, and ALP may play a role in the development and progression of T2DM and NAFLD.

Qingshen granule-medicated serum attenuates high glucose-induced epithelial-mesenchymal transition of HK-2 cells via inhibiting oxidative stress-mediated NF-κB signaling pathway / 中国病理生理杂志

AIM:To investigate whether Qingshen granules(QSG)-medicated serum inhibits oxidative stress-mediated NF-κB signaling pathway and attenuates epithelial-mesenchymal transition(EMT)of human proximal tubule epi?thelial HK-2 cells induced by high glucose. METHODS:The active components in QSG were analyzed by HPLC. The HK-2 cells were randomly divided into control group,mannitol group,high glucose group,low-dose QSG group,medium-dose QSG group,high-dose QSG group and pyrrolidine dithiocarbamate(PDTC)group. The morphological changes of the cells were observed by inverted phase contrast microscopy. MTT assay was used to detect the cell viability. Flow cytometry was used to detect the content of reactive oxygen species(ROS)in HK-2 cells. ELISA was used to detect the content of malondi?al dehyde(MDA)and the activity of superoxide dismutase(SOD). The DNA binding activity of nuclear factor-κB(NF-κB) p65 in HK-2 cells was detected by electrophoretic mobility-shift assay(EMSA). The protein expression of NF-κB p65, phosphorylated inhibitor of kappa B alpha(p-IκBα),inhibitor of kappa B kinase alpha(IKKα),monocyte chemoattractant protein-1(MCP-1)and intercellular adhesion molecule-1(ICAM-1)in HK-2 cells was detected by Western blot. Immuno?fluorescence staining was used to detect NF-κB p65 andα-smooth mucle actin(α-SMA)protein expression in HK-2 cells. RESULTS:Chlorogenic acid,berberine hydrochloride,plantamajoside,6,7-dimethoxycoumarin,epiberberine,copti?sine,lithospermicacid B,palmatine,leonurine hydrochloride,rheic acid and tanshinone ⅡA in QSG were preliminarily de?termined by HPLC. Compared with control group,the levels of ROS and MDA in HK-2 cells induced by high glucose in?creased(P<0. 05),while the activity of SOD decreased(P<0. 05). The protein levels of NF-κB p65,p-IκBα,IKKα, MCP-1,ICAM-1 andα-SMA were increased(P<0. 05). After intervened by QSG-medicated serum,the levels of ROS and MDA were decreased(P<0. 05),while the activity of SOD was increased(P<0. 05). The protein levels of NF-κB p65,p-IκBα,IKKα,MCP-1,ICAM-1 andα-SMA were decreased(P<0. 05). CONCLUSION:QSG-medicated serum inhibited oxidative stress-mediated NF-κB signaling pathway,thus attenuating the EMT of HK-2 cells induced by high glucose.

Application of mind mapping combined with scenario simulation teaching in probation teaching of abdominal trauma / 中华医学教育探索杂志

Objective:To explore the effect of mind mapping combined with scenario simulation teaching on probation teaching of abdominal trauma.Methods:The probation undergraduates from Batch 2017 five-year clinical medicine of Air Force Medical University were selected as research objects and randomly divided into experimental group ( n=98) and control group ( n=92). The experimental group was taught by mind mapping combined with scenario simulation teaching method, while the control group was taught by traditional teaching mode. After the end of the course, the effect of teaching was evaluated from two aspects: theoretical evaluation and teaching satisfaction evaluation. SPSS 19.0 was used for t test and chi-square test. Results:The results of theoretical test in the experimental group were significantly better than those of the control group [(84.03±8.99) vs. (78.53±8.97)], and the difference was statistically significant ( P<0.05). Compared with the control group, the experimental group had obvious advantages in learning interest, teamwork awareness and clear thinking, and achieved good teaching effect. Conclusion:Therefore, this teaching model helps to improve the teaching quality and provides some reference experience.

Hyperlipidemia and intestinal microflora distributions among flying personnel / 预防医学

Objective@#To investigate the characteristics of intestinal microflora among flying personnel with hyperlipidemia, so as to provide insights into prevention of hyperlipidemia among flying personnel. @*Methods @#Flying personnel diagnosed with hyperlipidemia in a sanatiorium from October 2020 to February 2021 were included in the hyperlipidemia group, while flying personnel with normal blood lipids during the same period served as controls. Subjects' age, family history, physical examinations and blood testing results were collected from both groups. Fecal samples were collected, and intestinal microflora was sequenced followed by bioinformatics analysis. The diversity and abundance of intestinal microflora were compared, and the key bacteria were screened using LEfSe analysis.@*Results@#There were 29 subjects in the hyperlipidemia group with a median age (interquartile range) of 34 (12) years and 25 subjects in the control group with a median age (interquartile range) of 30 (12) years, and all subjects were men. There were no significant differences between the two groups in terms of age, flight duration, smoking, family history of metabolic diseases and waist circumference (P>0.05). The Shannon diversity index of intestinal microflora was lower in the hyperlipidemia group than in the control group (Z=4.370, P=0.026), and there was a significant difference in the overall structure of intestinal flora between the two groups, which were clustered into two groups. LEfSe analysis identified Herbaspirillum, Atopobium and Eggerthella as key microorganisms in the hyperlipidemia group, and Agathobacter, Dialister, norank_Eubacterium_coprostanoligenes_group, Alloprevotella and unclassified Bacteroidales as key microorganisms in the control group.@*Conclusions@#The species diversity and relative abundance of intestinal microflora are lower in flying personnel with hyperlipidemia than in those with normal blood lipids. Herbaspirillum, Atopobium and Eggerthella may be the key bacteria contributing to hyperlipidemia among flying personnel.

Effect of Modified Shenling Baizhusan on Gastrointestinal Dysfunction and Protein-energy Wasting in Continuous Ambulatory Peritoneal Dialysis Patients / 中国实验方剂学杂志

ObjectiveTo observe and analyze the effect of modified Shenling Baizhusan on gastrointestinal dysfunction and protein-energy wasting （PEW） of continuous ambulatory peritoneal dialysis （CAPD） patients with the syndrome of spleen deficiency， blood stasis， and dampness. MethodA total of 66 CAPD patients with the above syndrome were randomized into the observation group and control group， 33 cases in each group. However， 3 cases in each group dropped out， finally leaving 30 cases in each group. Both groups received CAPD and conventional symptomatic treatment. On this basis， the observation group was given modified Shenling Baizhusan （1 bag/day， once in the morning and again in the evening， 12 weeks）， and the control group the bifidobacterium capsules （1.05 g/time， twice/day， 12 weeks）. Before and after treatment， the traditional Chinese medicine （TCM） syndrome score， gastrointestinal symptom rating scale （GSRS） score， and malnutrition-inflammation score （MIS） in two groups were recorded， and the levels of serum albumin （ALB）， prealbumin （PA）， transferrin （TRF）， gastrin-17 （G-17）， tumor necrosis factor alpha （TNF-α）， interferon-γ （IFN-γ）， and interleukin-10 （IL-10） were detected. Moreover， body mass index （BMI） was calculated. ResultAfter treatment， the alleviation of the TCM syndrome in the observation group was better than that in the control group （Z=-2.591， P<0.05）， and the TCM syndrome score in the observation group was lower than that in the control （P<0.05）. The symptom scores， MIS， and G-17 of the observation group were significantly decreased compared with those before observation and in the control group （P<0.05）. After treatment， the GSRS scores of the two groups were significantly lower than those before treatment （P<0.05）， particularly the observation group （P<0.05）. ALB， PA， TRF， and BMI of the observation group after treatment were increased compared with those before treatment and those of the control group after treatment （P<0.05）. After treatment， serum TNF-α and IFN-γ of the two groups were significantly reduced compared with those before treatment （P<0.05）， and the levels of the two in the observation group were significantly lower in the observation group than in the control group （P<0.05）. After treatment， IL-10 level of the observation group was higher than that before treatment and in the control group （P<0.05）. ConclusionThe modified Shenling Baizhusan can relieve the gastrointestinal dysfunction and PEW in CAPD patients with the syndrome of spleen deficiency， blood stasis， and dampness.

Macrophage Polarization and Anti-tumor Mechanism of Chinese Medicine：A Review / 中国实验方剂学杂志

Macrophages are natural immune cells with strong plasticity. The polarization of macrophages mainly responds to stimuli in the microenvironment by changing their phenotype and related functions. In recent years， studies have found that the polarization of macrophages is involved in the occurrence and development of various diseases such as bone arthritis， skin diseases， diabetes， coronary heart disease， breast cancer， colorectal cancer， and lung cancer， especially the metastasis of malignancies and drug resistance， through multiple signaling pathways， including nuclear factor kappa-B（NF-κB）， c-Jun N-terminal kinase（JNK）， protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， signal transducer and activator of transcription 6 （STAT6）， Wnt/β-catenin， and mammalian target of rapamycin （mTOR） and regulatory factors， such as granulocyte-macrophage colony-stimulating factor （GM-CSF）， interleukin （IL）-4， IL-10， transforming growth factor （TGF）-β， tumor necrosis factor（TNF）-α， and interferon-γ（IFN-γ）. Chinese medicine is also pivotal in the prevention and treatment of malignancies. In recent years， therefore， the specific anti-tumor mechanism of Chinese medicine and its active ingredients has become a research hotspot. The tumor microenvironment is crucial to the occurrence and development of tumors. The polarization of tumor-associated macrophages is involved in the proliferation， apoptosis， and metastasis of tumor cells. Therefore， targeted regulation of the polarization of tumor-associated macrophages is a potential target for clinical treatment of malignancies. Based on the research articles published in the past three years， this article reviewed macrophage polarization and the anti-tumor mechanism of Chinese medicine from four perspectives， i.e.， macrophage polarization， related pathways and regulatory factors of macrophage polarization， macrophage polarization and breast cancer， colorectal cancer， and lung cancer， and macrophage polarization and anti-tumor effects of Chinese medicine， active ingredients of Chinese medicine， and self-formulated prescriptions/classic prescriptions. This study is expected to provide certain ideas for the clinical treatment， basic research， and development of new Chinese medicine in the treatment of tumors.

Bazi Bushen Capsules on Anti-aging： A Review / 中国实验方剂学杂志

The decline of body function and senile diseases caused by aging seriously affect human health and life span， which is an important topic in the field of life science. Bazi Bushen capsules is a representative Chinese patent medicine for tonifying essence， invigorating Qi and anti-aging， guided by Qiluo doctrine， and essence， Qi and spirit theory. Previous pharmacological and clinical studies have confirmed that this preparation has the comprehensive advantages of anti-aging， and prevention and treatment of aging-related diseases. Among them， pharmacological studies showed that Bazi Bushen capsules had the effect of improving the appearance status of mice， improving the level of sex hormones， inhibiting the formation of atherosclerosis， improving cardiac function， improving learning and memory cognitive ability， improving neurological function， improving osteoporosis and muscle function， improving sperm count and quality. The mechanism was related to the up-regulation of the recombinant sirtuin （SIRT6） level， down-regulation of the levels of aging-related proteins p53 and p16， up-regulation of telomerase reverse transcriptase level， and alleviation of inflammation and oxidative response. Clinical studies have proved that it can improve the symptoms of patients with kidney essence deficiency， improve exercise ability， and improve the sexual function of impotence patients. Anti-aging research of Bazi Bushen capsules based on Qiluo doctrine fully embodies the new mode of academic innovation and transformation of traditional Chinese medicine （TCM） with the combination of "theory-new drug-experiment-clinic"， which has made a demonstration for the anti-aging research of TCM.

Research on Anti-aging Guided by Qiluo Doctrine / 中国实验方剂学杂志

Along with increasing degree of population aging globally， senility， good health and long life have become the focus of the world. Guided by Qiluo doctrine， an essence， Qi and spirit theory is proposed as below， essence is the origin of life， Qi is the impetus of life and spirit is the embodiment of life. Based on holistic view of kidney deficiency involving the five internal organs and injuries of the five internal organs definitely affecting the kidney， a mechanism of aging is proposed as below， deficiency of kidney essence is the foundation of aging， deficiency of promordial Qi is the key of aging and physical and spiritual loss is the manifestation of aging. It provides a theoretical guidance for anti-aging study of rejuvenating the elderly and making the strong person stronger. By virtue of the experiences in kidney-tonifying medication accumulated for more than two thousand years， Bazi Bushen capsules has been developed， which has anti-aging efficacy， including tonifying kidney， replenishing essence， coordinating Yin and Yang， supplementing primordial Qi and nourishing body and spirit. Experimental researches have demonstrated that Bazi Bushen capsules can improve overall aging and systemic aging， as well as prevent and treat aging related diseases. Preliminary clinical studies demonstrate that this capsules can enhance athletic ability and improve sexual function， and is expected to become a representative Chinese patent medicine of anti-aging. This paper addresses aging and anti-aging on the basis of Qiluo doctrine， in the hope of helping prevention and treatment of aging related diseases.

Dynamic control of ERG20 expression to improve production of monoterpenes by engineering Saccharomyces cerevisiae / 中国中药杂志

Monoterpenes are widely used in cosmetics, food, medicine, agriculture and other fields. With the development of synthetic biology, it is considered as a potential way to create microbial cell factories to produce monoterpenes. Engineering Saccharomyces cerevisiae to produce monoterpenes has been a research hotspot in synthetic biology. In S. cerevisiae, the production of geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) is catalyzed by a bifunctional enzyme farnesyl pyrophosphate synthetase(encoded by ERG20 gene) which is inclined to synthesize FPP essential for yeast growth. Therefore, reasonable control of FPP synthesis is the basis for efficient monoterpene synthesis in yeast cell factories. In order to achieve dynamic control from GPP to FPP biosynthesis in S. cerevisiae, we obtained a novel chassis strain HP001-pERG1-ERG20 by replacing the ERG20 promoter of the chassis strain HP001 with the promoter of cyclosqualene cyclase(ERG1) gene. Further, we reconstructed the metabolic pathway by using GPP and neryl diphosphate(NPP), cis-GPP as substrates in HP001-pERG1-ERG20. The yield of GPP-derived linalool increased by 42.5% to 7.6 mg·L~(-1), and that of NPP-derived nerol increased by 1 436.4% to 8.3 mg·L~(-1). This study provides a basis for the production of monoterpenes by microbial fermentation.

Construction of cell factories for high production of ginsenoside Rh_2 in Saccharomyces cerevisiae / 中国中药杂志

Ginsenoside Rh_2 is a rare active ingredient in precious Chinese medicinal materials such as Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Panacis Quinquefolii Radix. It has important pharmacological activities such as anti-cancer and improving human immunity. However, due to the extremely low content of ginsenoside Rh_2 in the source plants, the traditional way of obtaining it has limitations. This study intended to apply synthetic biological technology to develop a cell factory of Saccharomyces cerevisiae to produce Rh_2 by low-cost fermentation. First, we used the high protopanaxadiol(PPD)-yielding strain LPTA as the chassis strain, and inserted the Panax notoginseng enzyme gene Pn1-31, together with yeast UDP-glucose supply module genes[phosphoglucose mutase 1(PGM1), α-phosphoglucose mutase(PGM2), and uridine diphosphate glucose pyrophosphorylase(UGP1)], into the EGH1 locus of yeast chromosome. The engineered strain LPTA-RH2 produced 17.10 mg·g~(-1) ginsenoside Rh_2. This strain had low yield of Rh_2 while accumulated much precursor PPD, which severely restricted the application of this strain. In order to further improve the production of ginsenoside Rh_2, we strengthened the UDP glucose supply module and ginsenoside Rh_2 synthesis module by engineered strain LPTA-RH2-T. The shaking flask yield of ginsenoside Rh_2 was increased to 36.26 mg·g~(-1), which accounted for 3.63% of the dry weight of yeast cells. Compared with those of the original strain LPTA-RH2, the final production and the conversion efficiency of Rh_2 increased by 112.11% and 65.14%, respectively. This study provides an important basis for further obtaining the industrial-grade cell factory for the production of ginsenoside Rh_2.

Influence of normal tissue objective on intensity modulated radiation therapy for rectal cancer based on the Eclipse treatment planning system / 中国辐射卫生

Objective To analyze the dosimetric effect of the optimization tool, normal tissue objective (NTO), in Eclipse on the intensity modulated radiation therapy (IMRT) for postoperative patients with rectal cancer. Methods Twenty postoperative patients with rectal cancer were randomly selected. Based on the Eclipse treatment planning system, three IMRT plans were formulated for each patient, with manual NTO as the control group, and automatic NTO and no NTO as the other two groups. The dosimetric parameters of the target volume and organs at risk (OAR) and the monitor units (MU) were compared between the automatic NTO and no NTO groups and the control group under the same optimization conditions. Results Compared with the control group, the automatic NTO group showed a worse conformity index (CI) (t = 3.248, P < 0.05), a 0.6% higher Dmean of normal tissues (t = -3.678, P < 0.05), and no significant difference in the dose to OAR and the MU (P > 0.05); the no NTO group showed a worse CI (t = 16.716, P < 0.05), a better homogeneity index (t = 6.594, P < 0.05), a 3.19% higher Dmean of normal tissues (t = -8.560, P < 0.05), no significant difference in the dose to OAR except the small intestine with higher Dmax (P > 0.05), and a 3.95% increase in the MU. Conclusion From the dosimetry results of the target volume and OAR, the plans with manual NTO and automatic NTO, and without NTO can meet clinical needs, but the plan without NTO increases the hot spots outside the target volume and the MU as well as the Dmean of normal tissues. Manual NTO has no obvious advantages over automatic NTO which is recommended for the fixed-field IMRT of rectal cancer.

Comparison of intracardiac and upturned approach for total anomalous pulmonary venous connection / 中华胸心血管外科杂志

Objective:Analyze the effect of intracardiac method and upturning method in the treatment of infracardiac total anomalous pulmonary venous connection(TAPVC), to explore the surgical method of infracardiac TAPVC.Methods:From July 2011 to August 2019, 20 patients with infracardiac TAPVC were treated, including 12 cases with upturning method and 8 cases with intracardiac method. The cardiopulmonary bypass time, aortic cross-clamp time, delayed thoracic closure, ICU time, mechanical ventilation time, postoperative days and anastomotic flow rate were compared between the two groups.Results:There was no significant difference in cardiopulmonary bypass time, aortic cross-clamp time, delayed thoracic closure, ICU time and mechanical ventilation time between the two groups. The postoperative hospital stay in upturning group was significantly lower than that in intracardiac group [(14.7±2.9)days vs.(16.1±6.2)days, P<0.05], and the postoperative anastomotic velocity > 120 cm/s in intracardiac group was significantly less than that in upturning group(1 case vs. 7 cases, P<0.05). Two patients died in upturning group, but there was no significant difference compared with the intracardiac group. Conclusion:There is no significant difference between the two methods in the treatment of subcardiac TAPVC. The authors think that the exposure of the upturning methods is difficult, and the distortion of the anastomosis may be hidden trouble. The in situ anastomosis of the intracardiac method is not easy to make mistakes.

Laparoscopic or robotic serosa muscular layer circumferential incision combined with mucosal layer cutting and closure for gastrointestinal mesenchymal tumors at difficult sites of the stomach / 中华普通外科杂志

Objective:To evaluate the use of serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery for gastrointestinal mesenchymal tumors at difficult sites of the stomach.Methods:From Jul 2019 to Apr 2021, 18 gastric mesenchymal tumor patients undergoing serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery at the Department of Surgery, the Fourth Hospital of Hebei Medical University were retrospectively analyzed.Results:All 18 patients had successful surgery, including 7 cases of robotic surgery, 11 cases of laparoscopic surgery, and there was no conversion to open surgery. Tumors were at the gastric in cardia, 8 cases at the gastric body and lesser curvature in 4 cases, and at the gastric antrum in 6 cases, respectively. Eleven cases were of endogenous and 7 cases were of dumbbell type. The average operation time was (99±29) min, the intraoperative blood loss was (10±5) ml, the first time taking food per mouth was (2.0±1.0) d, and the postoperative hospital stay was (4.9 ± 1.2) d. Pathology showed gastrointestinal stromal tumor in 11 cases, leiomyoma in 5 cases and schwannoma in 2 cases. All were with negative margins. The average tumor diameter was (4.7±1.4) cm. The median follow-up time was 16.5 months, and there was no sign of tumor recurrence or metastasis.Conclusion:The serosa muscular layers circumferential incision combined with mucosal layer cutting and closure technique in laparoscopic or robotic surgery is a safe and feasible procedure for treating gastrointestinal mesenchymal tumor at difficult sites of the stomach.

A risk prediction model of conversion to open surgery during laparoscopic splenectomy and esophagogastric devascularization / 中华普通外科杂志

Objective:To establish a risk prediction model of conversion to open surgery during laparoscopic splenectomy and esophagogastric devascularization (LSED) and evaluate the impact of this conversion on patients' short-term prognosis.Methods:A total of 358 cirrhotic portal hypertension patients admitted to the Department of General Surgery , Second Affiliated Hospital, Air Force Military Medical University from Feb 2011 to Nov 2020 were retrospectively analyzed. All patients underwent attempted LSED. Univariate and least absolute shrinkage and selection operator (LASSO) Logistic regression were used to analyze the independent risk factors for conversion to laparotomy, and the R language was used to build a nomogram prediction model for conversion to laparotomy. The intraoperative and postoperative conditions of the two groups were compared.Results:A total of 358 patients were included in this study, of which 31(8.7%). patients were converted to open surgery. In univariate analysis, high MELD score, BMI ≥24 kg/m 2, history of upper abdominal surgery, red sign of the varicose, low platelet count and prolonged PT are risk factors for conversion . LASSO regression finally identified 5 factors: MELD, BMI, PLT, history of surgery, and red sign. In the nomogram prediction model the area under ROC curve was 0.831. The conversion led to longer operation time; increased blood loss; prolonged postoperative abdominal drainage , longer hospital stay, and increased perioperative complications ( t=-2.167, P=0.031; Z=-4.350, P<0.01; Z=-3.102, P=0.002; Z=-3.454, P=0.001; χ2=8.773, P=0.003). Conclusions:LASSO regression selected five indicators with greatest impact on intraoperative conversion: MELD, BMI, PLT, red sign, and previous history of abdominal surgery. The nomogram prediction model established has good prediction ability. Patients converted to open surgery had worse short-term outcomes.

Bioinformatics based analysis of key genes underlying the development of nonalcoholic fatty liver disease / 中华内分泌代谢杂志

Objective:To identify key genes and their potential biological mechanisms in the progression of non-alcoholic fatty liver disease (NAFLD) using bioinformatics technology.Methods:Genes differentially expressed in simple non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis (NASH) were analyzed by integrating NAFLD-related sequencing datasets GSE135251 and GSE167523 from the Gene Expression Omnibus (GEO) datebase. Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome signaling pathway analysis were performed. Key genes were identified by STRING database and Cytoscape3.7.2 software, and the expression of key genes under different fibrosis grades and activity scores was observed. In addition, the expression of key genes in different cell clusters was observed based on the single-cell RNA-seq dataset of NAFLD mice.Results:Bioinformatics methods were used to obtain 97 common differential genes in NAFLD from two datasets. GO functional enrichment analysis was mainly performed in Extracellular Matrix (ECM) tissues. The main signaling pathway is ECM-receptor interaction. Five key genes were identified based on PPI network and Cytoscape software: COL1A1, THBS2, CXCL8, THY1 and LOXL1. The expression of key genes was significantly positively correlated with fibrosis grade and activity score, indicating that they were closely related to the progression of NAFLD. These key genes are highly expressed in hepatic stellate cells (HSCs) and natural killer/T cells (NK/T cells).Conclusion:In this study, bioinformatics technology was used to identify five key genes that may be involved in the NAFL-NASH transformation, suggesting that the ECM-receptor interaction signaling pathway may be a key molecular mechanism of NAFLD disease progression.

Bladder-sparing treatment following noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy for muscle-invasive bladder cancer / 中华泌尿外科杂志

Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.

Tumor microenvironment responsive liposomes blocking CXCL12/CXCR4 pathway and synergistically enhancing immune efficacy of anti-PD-L1 / 药学学报

Blocking immune checkpoint programmed cell death receptor 1 (PD-1) or programmed death receptor-ligand 1 (PD-L1) can enhance anti-tumor activity of effector T cells. However, the lack of response in many patients to PD-1/PD-L1 therapy remains a question. Improving the immunosuppressive tumor microenvironment (TME) to enhance the efficacy of immune checkpoint inhibitors has become a promising cancer treatment strategy. We constructed a liposome system (PD-L1/siCXCL12-Lp) of CXCL12 siRNA and anti-PD-L1 peptide with matrix metalloproteinases (MMPs) responsiveness, which combined the TME regulation of siCXCL12 and the immune regulation of anti-PD-L1 peptide. All animal experiments were approved by the Biomedical Ethics Committee of Peking University. The authors found that PD-L1/siCXCL12-Lp directly down-regulated the expression of CXCL12 in vitro (33.8%) and in vivo (15.5%). It also effectively increased the ratio of CD8+/Treg by 20.0%, which helped the anti-PD-L1 peptide to better exert its immune effect. The combination therapy significantly inhibited tumor growth (52.08%) with great safety, which explored a new idea for cancer immunotherapy.

The relationship between the lipid profiles and inflammation in patients with sepsis / 中华危重病急救医学

Objective:To explore the relationship between the changes in the lipid profiles and the intensity of inflammatory response and disease severity in patients with sepsis, in order to find a biomarker that can quickly evaluate the condition and prognosis of sepsis.Methods:A retrospective analysis was performed on 449 patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from October 2019 to May 2021, and 355 patients without sepsis hospitalized in the same period served as the control. The general demographic data, blood lipid and other clinical indicators within 24 hours after admission were collected and compared between the two groups. Bivariate correlation study was used to analyze the relationship between blood lipid levels and inflammation indicators and severity of illness in patients with sepsis. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each blood lipid component on the 28-day mortality of patients with sepsis. According to the results of ROC curve analysis, the blood lipids were divided into two groups with different levels, and the Kaplan-Meier survival curve was used to compare the cumulative survival rates of the two groups without end-point event (the 28-day mortality was the end-point event).Results:Compared with non-septic patients, the levels of plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were significantly lower in patients with sepsis [TC (mmol/L): 2.93±1.33 vs. 4.01±1.14, HDL-C (mmol/L): 0.78±0.47 vs. 1.16±0.40, LDL-C (mmol/L): 1.53±1.00 vs. 2.71±0.98, all P < 0.05]. In patients with sepsis, plasma cholesterol levels were correlated with the degree of inflammation and severity of the disease to varying degrees, but the HDL-C had the strongest correlation with interleukin-6 (IL-6; r = -0.551, P = 0.000), procalcitonin (PCT, r = -0.598, P = 0.000), sequential organ failure assessment (SOFA; r = -0.285, P = 0.000). The ROC curve analysis showed that among all blood lipid components, HDL-C had the highest predictive value for 28-day mortality of sepsis patients, and the area under the ROC curve (AUC) was 0.718, when the best cut-off value was 0.69 mmol/L, the sensitivity and specificity were 67.3% and 65.2% respectively, and the positive predictive value and negative predictive value were 60.6% and 71.5% respectively. According to Kaplan-Meier survival curve analysis, the mortality of sepsis patients with HDL-C ≤ 0.69 mmol/L was significantly higher than the patients with HDL-C > 0.69 mmol/L, and the difference was statistically significant ( P < 0.000 1). In addition, the 28-day mortality [59.73% (135/226) vs. 28.70% (64/223)], the incidence of multiple organ dysfunction [41.15% (93/226) vs. 31.84% (71/223)], the probability of requiring mechanical ventilation and vasoactive drugs [mechanical ventilation: 56.64% (128/226) vs. 46.18% (103/223); vasoactive drugs: 54.42% (123/226) vs. 38.57% (86/223)], the positive rate of microbial culture [45.58% (103/226) vs. 35.43% (79/223)], and the probability of drug-resistant bacteria [19.91% (45/226) vs. 10.31% (23/223)] in the low HDL-C group of sepsis patients were all higher than the high HDL-C group, the differences were statistically significant (all P < 0.05). Conclusions:Plasma cholesterol levels, especially the HDL-C levels, can well reflect the intensity of inflammation and the severity of the disease in patients with sepsis. And the HDL-C levels can be used as a good biomarker for predicting the short-term prognosis of sepsis.

Analysis of specimen adequacy of fine needle non-aspiration cytology in thyroid nodules / 中华内分泌外科杂志

Objective:To investigate the occurrence of inadequate specimens of thyroid nodule fine needle non-aspiration cytology and its possible influencing factors.Methods:Clinical data of 1571 patients with FNAC of 1638 thyroid nodules were analyzed retrospectively, according to whether the FNAC specimen were adequate or not, all cases were divided into adequate group and inadequate group. The related influencing factors on inadequate specimen were analyzed by univariate analysis and multivariate logistic regression.Results:Inadequate specimens occurred in 301 of 1638 (18.4%) nodules. Logistic regression analysis showed that the influencing factors of overall specimen adequacy included operator experience ( P=0.00) , nodules size≤0.5 cm ( P=0.00) , eggshell calcification ( P=0.00) , and cystic ( P=0.00) . Excluding the impact of operator experience, the influencing factors of specimen adequacy included nodules size≤0.5 cm ( P=0.00) , eggshell calcification ( P=0.00) , and cystic ( P=0.00) . Conclusions:Operator experience, nodules size≤0.5 cm, cystic, together with eggshell calcification are influencing factors of specimen adequacy of fine needle non-aspiration cytology in thyroid nodules. For experienced operators, what restrict specimen adequacy is the limitation of FNAC technique. For inexperienced operators, what restrict specimen adequacy is operator’s experience.